Depressive and Other Adverse CNS Effects of Fluoroquinolones

Abstract

Fluoroquinolones (FQs) are widely used drugs around the world. This is a result of their broad spectrum of antibacterial activity, high bioavailability, and known efficacy. Since they appeared on the market, their prescribing frequency has gradually increased. In 2011, FQs became the third most prescribed class of antibiotics in the US. Widespread use of these drugs resulted in an increasing number of reported side effects. In 2016, the FDA warned about significant side effects, including mental disorders in the form of anxiety, psychotic symptoms, insomnia, and depression. Psychiatric adverse reactions to FQs occur with a frequency of 1 to 4.4% and the mechanism of their formation is not entirely clear. It is believed that the antagonistic effect of FQs on the GABA receptor or interaction with the main receptor for the glutamatergic system—NMDA—is responsible for this. The paper is a structured review of 68 selected publications and the latest summary of CNS adverse effects that occur during FQ use. Prescribers should be aware of the risk factors for FQ toxicity, including elderly patients with underlying medical conditions or receiving concomitant medication; however, these adverse events may also occur in other groups of patients.

Mechanisms of the Antineoplastic Effects of New Fluoroquinolones in 2D and 3D Human Breast and Bladder Cancer Cell Lines

“…CNS adverse effects of FQs have been shown to be facilitated by the co-administration of NSAIDs and other agents such as theophylline, and have been linked to the low-affinity inhibition of GABA-A receptors and/or to a competitive stimulation of the glutamate/NMDA receptor (for a comprehensive review, see [ 70 , 71 ]). Thus, possible interactions of novel FQs with drugs that may predispose to CNS adverse effects (e.g., NSAIDs, theophylline) should be investigated as well, in the frame of preclinical studies.…”

Safety of fluoroquinolones

“…FQs AEs related to central nervous system (CNS) are the second most frequent after gastrointestinal-related AEs. They are estimated to occur in 1–4.4% patients and range from mild (confusion, irritability, and insomnia) to severe (encephalopathy, seizures, suicidal depression, catatonia, psychosis, and mania) [ 19 , 20 ]. FQs have been associated with neurotoxicity through the inhibition of GABA (gamma-aminobutyric acid) and NMDA (N-methyl-D-aspartate) receptors.…”

“…FQs have been associated with neurotoxicity through the inhibition of GABA (gamma-aminobutyric acid) and NMDA (N-methyl-D-aspartate) receptors. In addition, FQs derivatives with unsubstituted heterocycles in position C7 seem more associated with CNS side-effects [ 2 , 20 ]. The similar chemical structures of certain substituents at position 7 (piperazine in ciprofloxacin and norfloxacin) of the quinolone nucleus and the chemical structure of GABA allows these FQs to compete and displace GABA from its receptor sites, possibly leading to overstimulation.…”

“…Los EAs de FQs relacionados con el sistema nervioso central (SNC) son los segundos más frecuentes después de los gastrointestinales. Se estima que ocurren en el 1-4,4% de los pacientes y varían de leves (confusión, irritabilidad e insomnio) a graves (encefalopatía, convulsiones, depresión suicida, catatonia, psicosis y manía) [19,20]. Las FQs se han asociado con neurotoxic[idad a través de la inhibición de los receptores GABA (ácido gamma-aminobutírico) y NMDA (N-metil-D-aspartato).…”

“…Las FQs se han asociado con neurotoxic[idad a través de la inhibición de los receptores GABA (ácido gamma-aminobutírico) y NMDA (N-metil-D-aspartato). Además, los derivados de FQs con heterociclos no sustituidos en la posición C7 parecen estar más asociados a efectos secundarios sobre el SNC [2,20]. La similitud estructural química de ciertos sustituyentes en la posición 7 (piperazina en ciprofloxacino y norfloxacino) del núcleo de la quinolona y la estructura química del GABA permiten que estas FQs compitan y desplacen al GABA de sus receptores, lo que posiblemente conduzca a una sobreestimulación.…”